Military Vaccine Studies: On Trial

Military Vaccine Studies: On Trial

As the VaxGen studies progressed, AIDS vaccine researchers moved on to the next big thing: the “prime boost.” A “prime” shot would produce killer cells, which target and destroy the cells invaded by viruses, while a second “boost” shot would trigger an antibody response.

The lead candidate for the priming shot came from Aventis Pasteur, where scientists stitched HIV genes into a harmless bird virus called canarypox. For the antibody boost, researchers turned once again to gp120. Although this struck some as illogical, no other potential antibody-boosting vaccine had yet proven its safety in hundreds of humans, and gp120’s proponents further reasoned that the two vaccines might somehow synergize with each other. The HIV Vaccine Trials Network, an NIH-funded group of academic researchers, and the U.S. Military HIV Research Program, run from the Walter Reed Army Institute of Research in Silver Spring, MD, drew up plans for two separate efficacy trials of the canarypox/gp120 strategy.

Backroom grumbling about these two new trials grew audible in January 2002, when AIDS immunologist John Moore of Cornell University’s Weill Medical College in New York City wrote a stinging commentary for Nature magazine. Moore had no quarrel with the prime-boost idea, but he questioned most every other aspect of the proposed trials. Moore charged that NIH and the military behaved like rivals and felt compelled to “shadow” each other. He further argued that it “would surely be prudent” to wait for results from the VaxGen gp120 efficacy trials then under way before launching new studies.

The next month, the HIV Vaccine Trials Network pulled the plug on its prime-boost study after small human trials of the canarypox vaccine showed that it wasn’t very good at stimulating killer cells. The military, however, stood by its decision to conduct its own $119-million prime-boost study in collaboration with Thailand’s Ministry of Public Health, Mahidol University, and the Thai Royal Army. In fact, the leading proponents of the Thai trial, including army colonel John McNeil, met quietly with outside consultants in Geneva in November 2002 to consider whether the design of the study should change if gp120 also failed as a solo agent. No, the group concluded, reasoning that the prime-boost strategy deserved to be tested anyway.

Predictably, the results of VaxGen’s efficacy trials, released in 2003, showed that gp120 conferred no more protection against HIV than a placebo. With solid evidence that their skepticism was warranted, gp120’s detractors – including Robert Gallo, whose lab first proved that HIV caused AIDS, and Neal Nathanson, the former head of the Office of AIDS Research at NIH – cranked up their objections to including the vaccine in the prime-boost study. In a Science magazine opinion piece published in January 2004, Gallo, Nathanson, Moore, and 19 other prominent AIDS researchers assailed the Thai trial and specifically complained about their exclusion from the Geneva meeting. The process “lacked input from independent immunologists and virologists who could have judged whether the trial was scientifically meritorious,” they wrote.

McNeil and three other gp120 proponents replied in another Science opinion piece that the trial couldn’t be stopped, since the United States had already made commitments to industry, the Thai government, and the people who had started to receive the vaccines. In a separate letter, an official at the Thai Ministry of Public Health added a revealing detail: the government of Thailand felt that the country would benefit from the study regardless of the results, since its scientists were gaining experience with HIV, its laboratories were being modernized, and general awareness of HIV/AIDS was rising.

And that, more or less, is where the controversy stands today. Last September, Thai and U.S. military scientists reported that they had enrolled more than 5,500 Thai volunteers in the study and that they would meet their goal of 16,000 participants within another year, with the entire study planned to conclude in 2009.

When scientific institutions seek robust criticism up front – as NIH did in 1994 – it doesn’t guarantee that everyone will walk away happy. But permitting this kind of dialogue does bow to a truth that seems to have escaped the Defense Department researchers in charge of the Thai trial: the later objections surface, the more they hurt. Had the prime-boost study’s organizers invited a few well-known, sharp-edged basic researchers to take part in the study’s design, they might still have decided not to change their basic plan. But they wouldn’t have had nearly two dozen leading scientists in the field publicly accusing them of playing ostrich.

Indeed, when the stakes are as high as they are in the search for an AIDS vaccine, it’s worth striving to keep the peace in constituent communities, even if it means inviting your enemies to the table. But that’s a battle plan that simply runs counter to the culture at the Department of Defense.